Bayer HealthCare Pharmaceuticals, Inc., Wayne, NJ 07470, USA.
Value Health. 2013 Jul-Aug;16(5):872-90. doi: 10.1016/j.jval.2013.03.1628. Epub 2013 Jul 10.
New therapies have attempted to improve on efficacy outcomes observed with docetaxel in patients with metastatic prostate cancer (MPC) who are hormone-therapy refractory or castration-resistant. In addition to the efficacy, patient-reported outcomes (PROs) and tolerability need to be assessed to define treatment benefit, as PROs measure the patient's subjective experience and can be correlated with hard outcomes. The main objective of this study was to evaluate the survival benefit of new therapies and secondary efficacy-related outcomes. Assessment of the number of studies reporting PROs and tolerability was also conducted.
A predefined search strategy was conducted on major academic/governmental databases and conference proceedings (2007-2011). Exclusion criteria were applied.
Of 77 studies identified, 26 (34%) evaluated survival as an end point; 14 (18%) assessed PROs/tolerability. In chemotherapy-naive patients (no/minimal symptoms), median overall survival (OS) was 26 months for sipuleucel-T. In relapsed patients, the survival benefit of cabazitaxel/abiraterone was 15 months and that of enzalutamide was 18 months. Denosumab prolonged time to first on-study skeletal-related event (20.7 months denosumab, 17.1 months zoledronic acid; P = 0.0002, noninferiority; P = 0.008, superiority). Similar benefit was documented with radium-223, a new bone-targeted α-particle-emitting radiopharmaceutical. Radium-223 also significantly improved the OS (two-sided P = 0.00185). Specific to PROs, they were incorporated primarily as secondary end points, and improvements in pain response (most commonly evaluated) were variable among the agents. Last, the therapies were associated with unique toxicities requiring careful consideration.
The results of this review demonstrate that the therapeutic landscape of MPC has changed dramatically and many therapies in MPC now show OS improvements of about 4 months in the postdocetaxel setting.
新疗法试图改善多西他赛治疗激素难治或去势抵抗转移性前列腺癌（MPC）患者的疗效。除了疗效之外，还需要评估患者报告的结果（PROs）和耐受性，以确定治疗效果，因为 PROs 衡量患者的主观体验，并可以与硬性结果相关联。本研究的主要目的是评估新疗法的生存获益和次要疗效相关结果。还评估了报告 PROs 和耐受性的研究数量。
在主要的学术/政府数据库和会议记录（2007-2011 年）上进行了预先确定的搜索策略。应用了排除标准。
在确定的 77 项研究中，26 项（34%）将生存作为终点进行评估；14 项（18%）评估了 PROs/耐受性。在化疗初治患者（无症状或症状轻微）中，sipuleucel-T 的中位总生存期（OS）为 26 个月。在复发患者中，卡巴他赛/阿比特龙的生存获益为 15 个月，恩杂鲁胺为 18 个月。地舒单抗延长了首次研究相关骨骼事件的时间（地舒单抗 20.7 个月，唑来膦酸 17.1 个月；P=0.0002，非劣效性；P=0.008，优效性）。新型骨靶向α 粒子发射放射性药物镭-223 也记录到了类似的获益。镭-223 还显著改善了 OS（双侧 P=0.00185）。具体到 PROs，它们主要作为次要终点纳入，并且各药物的疼痛反应改善情况各不相同。最后，这些疗法与需要仔细考虑的独特毒性相关。
本综述的结果表明，MPC 的治疗格局发生了巨大变化，许多 MPC 疗法现在在后多西他赛治疗中显示出大约 4 个月的 OS 改善。
